getting to goal
TRANSCRIPT
-
7/30/2019 Getting to Goal
1/57
Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management
of Diabetes in Canada
This material has been reviewed by the Canadian Diabetes Association for its medical and scientific accuracy.Presence of the Canadian Diabetes Association Partners in Progress mark does not constitute an endorsement of the products or services of GlaxoSmithKline Inc.
Getting to Goalin Type 2 Diabetes
-
7/30/2019 Getting to Goal
2/57
1 Harris S, et al, The Diabetes in Canada Evaluation (DICE) Study, ADA 2003, 2162-PO2 Harris MI, et al. Diabetes Care1999; 22:403408.
P
ercentageofsubjects
0
20
40
60
80
100
7%
A1C (%)
US (1988-1994)2
Many patients have inadequate glycemic control
38%
62%
P
ercentageofs
ubjects
0
20
40
60
80
100
< 7% 7%
A1C (%)
CAN (2003)1
50% 50%
-
7/30/2019 Getting to Goal
3/57
Years T2DM
Proportion of patients with A1C > 7.0increases with duration of type 2 diabetes
-
7/30/2019 Getting to Goal
4/57
Proportion of patients with hypertensionincreases with duration of type 2 diabetes
Years T2DM
-
7/30/2019 Getting to Goal
5/57
Proportion of patients with dyslipidemiaincreases with duration of type 2 diabetes
Years T2DM
-
7/30/2019 Getting to Goal
6/57
Proportion of patients with cardiovascular diseaseincreases with duration of type 2 diabetes
Years T2DM
-
7/30/2019 Getting to Goal
7/57
Proportion of patients with microvascular diseaseincreases with duration of type 2 diabetes
Years T2DM
-
7/30/2019 Getting to Goal
8/57
The evolution of management guidelines
Studies including UKPDS have highlighted the
importance of glycemic control in reducing complications
New guidelines include tighter targets for glycemic control Guidelines recognize importance of treating all aspects
of the condition
Current guidelines therefore include targets for
glycemic control
lipid levels
blood pressure
-
7/30/2019 Getting to Goal
9/57
Adapted from Stratton IM, et al. UKPDS 35. BMJ2000; 321:405412.
UKPDS: decreased risk of diabetes-related complications
associated with a 1% decrease in A1C
Percentagedecrease
inrelativerisk
corre
spondingtoa1%d
ecreaseinHbA1C
**
Any
diabetes-
related
endpoint
21%
**
Diabetes-
related
death
21% **
All
cause
mortality
14%
*
Stroke
12%
**
Peripheral
vascular
disease
43%
**
Myocardialinfarction
14%
**
Micro-
vascular
disease
37%
**
Cataract
extraction
19%
Observational analysis from UKPDS study data
Lower extremity amputation or fatal peripheral vascular disease
*P= 0.035; **P< 0.0001
-
7/30/2019 Getting to Goal
10/57
Stratton IM, et al. UKPDS 35. BMJ2000; 321:405412.
UKPDS: the benefits of improved
glycemic control
Improved glycemic control significantly reduces risk
of diabetes-related complications
UKPDS results indicated that a 1% reduction in A1Cwould reduce the risk of microvascular complications
by 37%, but have less effect (16%) on
macrovascular complications
Further improvement in sustained glycemic controland reduction in the burden of cardiovascular
disease are needed
-
7/30/2019 Getting to Goal
11/57
06
7
8
9
2 4 6 8 10
A1C(%)
Years from randomization
Upper limit of of normal = 6.2%
ConventionalGlyburideChlorpropamideMetforminInsulin
0
UKPDS demonstrated loss of glycemic
control with all agents studied
UK Prospective Diabetes Study Group. UKPDS 34. Lancet1998; 352:854865.
Overweight patients
Cohort, median values
-
7/30/2019 Getting to Goal
12/57
Turner RC, et al. UKPDS 49. JAMA 1999;281:20052012.
100
Years from randomization
3 6 90
20
40
60
80
3 6 9 3 6 9 3 6 9
Diet Insulin MetforminSulfonylurea
Overweight patients
Proportionofp
atients(%)
50%
Proportion of patients with A1C < 7.0% onmonotherapy at 3, 6 and 9 years
Error bars = 95% CI
-
7/30/2019 Getting to Goal
13/57
The UKPDS demonstrated progressive
decline of-cell function over time
100
80
60
40
P< 0.0001
HOMA model, diet-treated n = 376
Time from diagnosis (years)
100
-cellfunctio
n(%) 80
60
40
20
0
Start of treatment
Adapted from Holman RR. Diabetes Res Clin Pract1998; 40 (Suppl.):S21S25.
10 9 8 7 6 5 4 3 2 1 1 2 3 4 5 6
-
7/30/2019 Getting to Goal
14/57
Canadian Diabetes Association
2003 Clinical Practice Guidelinesfor the Prevention and Management
of Diabetes in Canada
Glycemic Targets
-
7/30/2019 Getting to Goal
15/57
CMAJ 1998; 159 (8 Suppl):S1-29
1998 CDA Treatment Targets
Level
Ideal(normalnondiabetic)
Optimal*(target goal) Suboptimal
(action maybe required)
Inadequate
(actionrequired)
GlycatedHb(% of upperlimit)e.g., HbA1cassay
10
Glucose level1-2 h after meal(mmol/L)
4.4-7 5.0-11 11.1-14 >14
Hb = hemoglobin
*These levels are likely related to minimal long-term complications but may be impossible to achieve in most paients with type 1 diabetes with current therapies
Attainable in the majority of people with diabetes but may not be adequate to prevent compicationsThese levels are related to a markedly increased risk of long-term complications, requiring a reassessment and readjustment of therapy
-
7/30/2019 Getting to Goal
16/57
A1C**(%)
FPG/preprandial PG(mmol/L)
2-hour postprandial PG(mmol/L)
Target for most patients 7.0 4.0-7.0 5.0-10.0
Normal range(considered for patientsin whom it can beachieved safely)
6.0 4.0-6.0 5.0-8.0
A1C = glycosylated hemoglobin
DCCT = Diabetes Control and Complications Trial
FPG = fasting plasma glucose
PG = plasma glucose
2003 CDA Recommended Targets for
Glycemic Control
-
7/30/2019 Getting to Goal
17/57
Components of Glycemic Control
2 h. PostprandialPlasma Glucose
5-10 mmol/L5-8 mmol/L*
Fasting/PreprandialPlasma Glucose
4-7 mmol/L4-6 mmol/L*
A1C
-
7/30/2019 Getting to Goal
18/57
Canadian Diabetes Association
2003 Clinical Practice Guidelinesfor the Prevention and Management
of Diabetes in Canada
Management of Hyperglycemia
in Type 2 Diabetes
-
7/30/2019 Getting to Goal
19/57
Lifestyle Intervention
The first step in treating type 2 diabetes
Nutrition therapy and exercise can improve glycemic control
Success of lifestyle intervention related to:
patients initial fasting plasma glucose level
amount of weight loss achieved by patient
Only a minority of patients are able to attain treatment
targets using lifestyle intervention alone.
-
7/30/2019 Getting to Goal
20/57
UKPDS 7: Response of FPG to Diet
Therapy in Newly Diagnosed Patients
N= 3044, newly diagnosed patients
FPG at diagnosis 12.1+/- 3.7 mmol/L
Diet counseling
Patients with FPG 10-12 mmol/L needed reduction of 28%ideal body weight; to attain FPG
-
7/30/2019 Getting to Goal
21/57
Antihyperglycemic Agents
-
7/30/2019 Getting to Goal
22/57
Glucose (G)
Insulin
I
I
I
Adipose tissue
Liver
Pancreas
Muscle
Gut
Carbohydrate
Stomach -glucosidase inhibitors
Insulinsecretagogues
Biguanides
Thiazolidinediones
Primary Sites of Action of Oral
Antihyperglycemic Agents
Adapted from Kobayashi M. Diabetes Obes Metab1999; 1 (Suppl. 1):S32S40.Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab1999; 13:309329.
-
7/30/2019 Getting to Goal
23/57
Key Recommendations
Antihyperglycemic agents should be initiated if glycemic targetsnot met after 2-3 months of lifestyle intervention
Antihyperglycemic agents should be started concomitantly withlifestyle if A1C levels are greater than 9%
The lag period before adding other agent(s) should be kept to aminimum to achieve glycemic targets within 6-12 months
Unless contraindicated, metformin should be used first line;
other agents should be considered in the order they appear inthe treatment algorithm
Insulin therapy should be initiated if targets cannot be achievedwith lifestyle changes and oral therapy
-
7/30/2019 Getting to Goal
24/57
Diet/exercise
Oralmonotherapy
Oralcombination
Insulin
Early aggressivecombination therapy as required
Stepwise treatment
Oral+/- insulin
New Treatment Options for
Type 2 Diabetes
-
7/30/2019 Getting to Goal
25/57
Management of Hyperglycemia in
Type 2 Diabetes
Clinical assessment and initiation of nutrition and physical activity
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
26/57
Add a drug from a different classor
Use insulin alone or in combination with:
biguanide insulin secretagogue
insulin sensitizer* alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
If not at target
* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin iscurrently not an approved indication in Canada.
Overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
27/57
Dose-Effect RelationshipDose-Effect RelationshipDose-Effect Relationship
Riddle M. Combiningsulfonylureas and other oral agents.Am J of Med. 2000; 108(6A):15S-22S.
Graph of theoretical dose-effect relationship for many drugs, showing thathalf-maximal dosages yield far more than 50% of the therapeutic effectsand that side effects can increase as the dosage nears maximal levels.
Maximal
Half-maximal
Half-maximal Maximal
Therapeutic effect
Side effect
Effect
Dose
-
7/30/2019 Getting to Goal
28/57
Dose-Response CurveDose-Response CurveDose-Response Curve
Riddle M. Combiningsulfonylureas and other oral agents.Am J of Med. 2000; 108(6A):15S-22S.
Dose-response curve showing GI related effects
30
20
10
0 500 1000 1500 2000 25000
0.5
1.0
1.5
2.0
Dose
GIDistress
Patients(%)
Reductionvs.placebo,
HbA1
c(%)
-
7/30/2019 Getting to Goal
29/57
Non-overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
30/57
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agents from different classes
biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor
Add an oral antihyperglycemic agentfrom a different class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
If not at target
* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is
currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)
L
I
F
E
S
T
Y
L
E
-
7/30/2019 Getting to Goal
31/57
Marked hyperglycemia (A1C 9.0%)
Basal and/or preprandial insulin
* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is
currently not an approved indication in Canada.* *If using preprandial insulin, do not add an insulin secretagogue.
L
I
F
E
S
T
Y
L
E
Intensify insulin regimen or add
biguanide insulin secretagogue** insulin sensitizer*
alpha-glucosidase inhibitorTimely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
If not at target
Cli i l t d i iti ti f t iti d h i l ti it
-
7/30/2019 Getting to Goal
32/57
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
33/57
A1C 9%
Consider insulin at any stage of treatment
Vascular protection to further reduce cardiovascular risk
Key Changes
-
7/30/2019 Getting to Goal
34/57
Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management
of Diabetes in Canada
This material has been reviewed by the Canadian Diabetes Association for its medical and scientific accuracy.
Presence of the Canadian Diabetes Association Partners in Progress mark does not constitute an endorsement of the products or services of GlaxoSmithKline Inc.
Getting to Goalin Type 2 Diabetes
-
7/30/2019 Getting to Goal
35/57
Supplementary Slides:Key Recommendations
-
7/30/2019 Getting to Goal
36/57
In people with type 2 diabetes, if glycemic targets are
not achieved using lifestyle management within 2 to 3
months, antihyperglycemic agents should be initiated[Grade A, Level 1A ]. In the presence of marked
hyperglycemia (A1C > 9.0%), antihyperglycemic
agents should be initiated concomitant with lifestyle
counselling [Grade D, Consensus].
Recommendation 1
-
7/30/2019 Getting to Goal
37/57
If glycemic targets are not attained when a single
antihyperglycemic agent is used initially, an
antihyperglycemic agent or agents from otherclasses should be added. The lag period before
adding other agent(s) should be kept to a minimum,
taking into account the pharmacokinetics of the
different agents. Timely adjustments to and/oradditions of antihyperglycemic agents should be
made in order to attain target A1C within 6 to 12
months [Grade D, Consensus].
Recommendation 2
-
7/30/2019 Getting to Goal
38/57
Recommendation 3
This choice of antihyperglycemic agent(s) should takeinto account the individual and the following factors:
Unless contraindicated, a biguanide (metformin)
should be the primary drug used in overweight patients
[Grade A, Level 1A];and
Other classes of antihyperglycemic agents may
be used either alone or in combination to attain
glycemic targets, with consideration given to theinformation in Table 1 and Figure 1 [Grade D,
Consensus for the order of antihyperglycemic agents
listed in Figure 1].
-
7/30/2019 Getting to Goal
39/57
Recommendation 4
In people with type 2 diabetes, if individual treatment
goals have not been reached with a regimen of
nutrition therapy, physical activity and sulfonylurea[Grade A, Level 1A], sulfonylurea plus metformin
[Grade A, Level 1A]or other oral antihyperglycemic
agents [Grade D, Consensus], insulin therapy should
be initiated to improve glycemic control.
-
7/30/2019 Getting to Goal
40/57
Recommendation 5
Combining insulin and the following oral antihyperglycemic
agents (listed in alphabetical order) has been shown to be
effective in people with type 2 diabetes:
alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A]
biguanide (metformin) [Grade A, Level 1A]
Insulin secretagogues (sulfonylureas) [Grade A, Level 1A]
Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]
(The combination of an insulin sensitizer plus insulin is
currently not an approved indication in Canada.)
-
7/30/2019 Getting to Goal
41/57
Recommendation 6
Insulin may be used as initial therapy in type 2 diabetes
[Grade A, Level 1A], especially in cases of marked
hyperglycemia (A1C > 9.0%) [Grade D, Consensus].
-
7/30/2019 Getting to Goal
42/57
Recommendation 7
To safely achieve optimal postprandial glycemic
control, mealtime insulin lispro or insulin aspart is
preferred over regular insulin [Grade B, Level 2].
-
7/30/2019 Getting to Goal
43/57
Recommendation 8
When insulin given at night is added to oral
antihyperglycemic agents, insulin glargine may be
preferred over NPH to reduce overnighthypoglycemia [Grade B, Level 2]and weight gain
[Grade B, Level 2 ].
-
7/30/2019 Getting to Goal
44/57
Recommendation 9
All individuals with type 2 diabetes currently using or
starting therapy with insulin or insulin secretagogues
should be counselled about the recognition andprevention of drug-induced hypoglycemia [Grade D,
Consensus].
-
7/30/2019 Getting to Goal
45/57
Supplementary Slides:Alternate Animation for
Treatment Algorithm
Clinical assessment and initiation of nutrition and physical activity
-
7/30/2019 Getting to Goal
46/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
47/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
48/57
Add a drug from a different classor
Use insulin alone or in combination with:
biguanide insulin secretagogue
insulin sensitizer* alpha-glucosidase inhibitor
Overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
49/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
50/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
51/57
Add a drug from a different classor
Use insulin alone or in combination with:
biguanide
insulin secretagogueinsulin sensitizer* alpha-glucosidase inhibitor
Non-overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
52/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
53/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
54/57
Add an oral antihyperglycemic agentfrom a different class or insulin*
Marked hyperglycemia (A1C 9.0%)
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
2 antihyperglycemic agents from different classes
biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor
If not at target
* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is
currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)
L
I
F
E
S
T
Y
L
E
Clinical assessment and initiation of nutrition and physical activity
-
7/30/2019 Getting to Goal
55/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
56/57
Mild to moderate hyperglycemia (A1C
-
7/30/2019 Getting to Goal
57/57
Marked hyperglycemia (A1C 9.0%)
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
Basal and/or preprandial insulin
If not at target
Intensify insulin regimen or add
biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitor
L
I
F
E
S
T
Y
L
E